The current lack of effective pharmacological treatments for managing clinical symptoms in Alzheimer’s dementia highlights the urgent need for developing non-pharmacological interventions in the field. Here we report a phase II randomized controlled trial that examined the immediate and mid-term effect of a cognitive process based training on multiple cognitive domains in mild cognitive impairment. We found robust intervention effect on processing speed/attention and working memory. These cognitive improvements were associated with both activation changes and network changes involving ACC, a hub for maintaining successful cognitive aging. These results provide new insights about non-pharmacological interventions in preventing dementia.